Investigations for Diabetes Mellitus

Dr Devika Dhabe

Glucose is essentially used as a screening parameter. Values are highly diet dependent and drug intake influence the results. The main advantage is that it is one of the most standardised parameters, that even patients can self determine the results by home monitoring metres. Glucose can be estimated chemically and enzymatically. If the fasting blood glucose value is more than 126 mg/dl or the random blood glucose value is more than 200 mg/dl, then it is considered to be a case of diabetes.

Glucose Tolernce Test: (GTT)

This test is used to measure the glucose tolerance in a person. The blood is drawn at intervals of 30 mins each. The first sample is fasting, at 30 mins, 60 min, 120 mins and 180 mins. In all five samples are collected.

The most important role of GTT is to help in the investigation of symptomless glycosuria. It also helps in diagnosing minor cases of DM. A diminished GTT indicates the decreased ability of the body to utilise glucose, thus in turn helping in the diagnosis of diabetes mellitus. An increased GTT indicates the ability to utilise more glucose. It leads to decreased endocrine activity. Seen in hypothyroidism, hypoadrenalism, and hypopituitrism.

Glycosylated Haemoglobin

Of all the glycated forms of Hb, HbA1c is the most stable. More than 80 per cent of the glycated form is the HbA1c. Hence, its measurement is taken to be the ideal parameter to understand the “Long term diabetic control”. This is the most important tool for monitoring diabetes. This test refers to the hemoglobin component formed by interaction with glucose, since half life of RBCs is approximately 120 days; a single HbA1c determination can give information about glycemic control in the preceding 8-12 weeks.

It is estimated by HPLC method, which is considered to be gold standard. The advantage is that this test does not require any dietary preparations, has low sensitivity but high specificity compared to oral glucose tolerance test.

Microalbumin (MAU)

MAU as the name suggests, is the first warning signal to an impending “Nephropathy” - if attention is not paid to keep diabetes under control. Microalbumin is present in 25 per cent of patients with type I disease and 36 per cent patients with type II disease. Patients with microalbuminuria have a greater risk for developing renal failure, vascular damage and risk for cardiovascular damage. It can be estimated by immunoturbidometry and nephelometry: 30 – 40 per cent of Type I {IDDM} diabetes mellitus develop diabetic nephropathy with a strong rise in incidence after 15 years duration of diabetes.

Insulin

This test is used for determination of concentration of bioavailable insulin in the patients. Total insulin exists in free and bound form. In patients without insulin antibodies, total and free levels are similar, but in patients with insulin antibodies total insulin levels are dependant on the binding capacity of the circulating endogenous insulin antibody and availability of insulin to bind to antibody sites. This test is used to determine dosage of IDDM with insulin antibodies. Free insulin measurement helps in interpreting blood sugar concentration and its relationship to insulin injections in insulin treated pts with insulin antibodies. Elevated blood glucose with low free insulin level indicates insufficient insulin for adequate control. Low blood glucose with high free insulin level indicates the need to change the dosage

Insulin Antibodies

Most common antibodies are IgG, IgM, IgA & IgE Abs have been reported. These antibodies are generally seen in pre-Type I DM as well as DM pts with exogenous bovine or human porcine insulin. Widespread use of human insulin & improved purity of animal insulin has led to significant decrease in insulin antibodies.

Free Insulin

Increased levels of free insulin are seen:

• Exogenous insulin
• Insulinoma
• Insulin resistance
• Type II DM.

Proinsulin

Proinsulin is produced in beta cells of pancreas and cleaved into insulin and C-peptide before release into circulation. Only 2-3 percent of proinsulin escapes the conversion and is secreted into blood. Proinsulin is produced in beta cells of pancreas and cleaved into insulin and C-peptide before release into circulation.

Increased levels are seen in

• Insulinomas
• Severe hypoglycemic hypoinsulinomas
• Hyperproinsulinemia.

Proinsulin inhibits hepatic production of glucose thus useful in type II DM.TG & HDL concentrations improve with proinsulin It is used as agonist with insulin due to longer elimination time ½ life and lower metabolic rate. Thus Proinsulin serves as analogue to insulin to retard the complications of Type II DM.

GAD Antibodies

GAD-65 Antibodies: GAD is known as Glutamic Acid Decarboxylase. They are detected in approximately 90 per cent of patients who are newly diagnosed of Type I DM and 80 per cent of pre-diabetic individuals and first degree relative of patients with IDDM.

C-Peptide

C-peptide is cleaved from proinsulin and released into circulation in the course of insulin biosynthesis. C-peptide is used for assessment of pancreatic islet cell function. Type II DM is associated with abundant C-peptide secretion whereas Type I DM has little or no C-peptide.

The writer is pathologist at NPIL and Dr Phadke’s Path Lab, Mumbai